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Aggrecan protects cartilage collagen from proteolytic cleavage
Michael A Pratta1, Wenqing Yao, Carl Decicco
1Bristol Myers-Squibb Pharmaceutical Company, Wilmington, Delaware 19898, USA. michael_a_pratta@gsk.com
The Journal of Biological Chemistry
|August 2, 2003
Summary
Aggrecan protects cartilage collagen from degradation in osteoarthritis. Inhibiting aggrecanase, an enzyme that breaks down aggrecan, also protects collagen, suggesting a therapeutic approach for cartilage protection.
Area of Science:
- Biochemistry
- Biomaterials Science
- Rheumatology
Background:
- Osteoarthritis involves degradation of cartilage matrix components, specifically type II collagen and aggrecan.
- Proteolytic enzymes like matrix metalloproteinases (MMPs) and aggrecanases are implicated in this degradation process.
Purpose of the Study:
- To investigate the protective role of aggrecan against collagen degradation in cartilage.
- To evaluate the efficacy of selective MMP and aggrecanase inhibitors in preventing cartilage matrix breakdown.
Main Methods:
- Incubation of freeze-thawed cartilage with and without aggrecan with MMP-1.
- Culture of interleukin-1-stimulated bovine nasal cartilage explants.
- Treatment of explants with selective MMP and aggrecanase inhibitors at different time points.
Main Results:
- Collagen was degraded in aggrecan-depleted cartilage but protected in intact cartilage.
- Selective MMP inhibitors prevented collagen degradation without affecting aggrecan degradation.
- Aggrecanase inhibitors blocked both aggrecan and collagen degradation, suggesting aggrecan's protective role.
Conclusions:
- Aggrecan plays a crucial role in protecting cartilage collagen from proteolytic degradation.
- Targeting aggrecanases with inhibitors may offer a therapeutic strategy for overall cartilage protection in osteoarthritis.